ALLELIC VARIATION IN THE VITAMIN-D-RECEPTOR INFLUENCES SUSCEPTIBILITYTO IDDM IN INDIAN-ASIANS

Vitamin D has important immunomodulatory properties and prevents devel opment of diabetes mellitus in an animal model of insulin-dependent di abetes (IDDM). We have studied the vitamin D receptor locus as a candi date for genetic susceptibility to IDDM in Southern Indian families. W e found evidence for an association of one particular vitamin D recept or allele with IDDM susceptibility in this community. Ninety-three Sou th Indian families consisting of available parents and an affected off spring were genotyped for three vitamin D receptor polymorphisms using the restriction enzymes TaqI, ApaI and BsmI as well as an adjacent mi crosatellite located to 12q14 (D12S85). Transmission disequilibrium te sting analysis was used to assess preferential transmission of polymor phic markers and haplotypes with IDDM. There was significant excess tr ansmission of vitamin D receptor alleles containing the BsmI restricti on site to affected offspring in these families (p = 0.016). No associ ation was found between D12S85 and IDDM. This study suggests that a po lymorphism within or close to the vitamin D receptor gene may modify s usceptibility to IDDM in this ethnic group.